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Piezoresistive silicon cantilevers fabricated by ion implantation are frequently used for force, displacement, and chemical sensors due to their low cost and electronic readout. However, the design of piezoresistive cantilevers is not a straightforward problem due to coupling between the design parameters, constraints, process conditions, and performance. We systematically analyzed the effect of design and process parameters on force resolution and then developed an optimization approach to improve force resolution while satisfying various design constraints using simulation results. The combined simulation and optimization approach is extensible to other doping methods beyond ion implantation in principle. The optimization results were validated by fabricating cantilevers with the optimized conditions and characterizing their performance. The measurement results demonstrate that the analytical model accurately predicts force and displacement resolution, and sensitivity and noise tradeoff in optimal cantilever performance. We also performed a comparison between our optimization technique and existing models and demonstrated eight times improvement in force resolution over simplified models.